When administered orally, the piperidinesulfamylureas disclosed in the above-mentioned application function as hypoglycemic agents. Particularly useful are those compounds in which the piperidine ring is substituted in the 4-position with various 2-pyridylamidoethyl radicals. Because of their remarkable ability to reduce blood sugar levels with a minimum of side effects, these compounds are particularly useful in the treatment of diabetes mellitus and therefore, a safe, economic method for their production is highly desirable.
Previously, 2-aminoethylpyridine was reacted with phthalic anhydride to form N-[2-(4-pyridyl)-ethyl]phthalimide which was then reduced with hydrogen in the presence of an anhydrous acid and a catalyst to yield N-[2-(4-piperidyl)-ethyl]phthalimide. Said phthalimide was then reacted with sulfamide to produce 4-(2-phthalimidoethyl)-1-piperidine sulfonamide. The conversion of the aminoethyl function to the phthalimidoethyl function permits the sulfamide to react only with the piperidine nitrogen. To proceed further with the synthesis, the phthalimide must be cleaved to give the primary amine. Though many other reagents were tried, this reaction could be best effected with anhydrous hydrazine, a highly explosive compound which is extremely dangerous to use in commercial-scale syntheses. The product of the hydrazine reaction is 4-(2-amino-ethyl)-1-piperidine sulfonamide which was then contacted with an appropriate substituted pyridyl acid chloride to yield a 4-(2-pyridylamidoethyl)-1-piperidine sulfonamide which was then elaborated as outlined below to yield the desired hypoglycemic agent.